Heparin

Heparin acts immediately to inhibit thrombin (factor IIa), and factors Xa and IXa. The drug can be given either subcutaneously or intravenously but must achieve a plasma level > 0.2U/ml to have its optimum effect in treating active thrombosis. Lower doses of heparin are used to prevent thrombosis. Heparin is used to treat unstable angina and to prevent and treat venous thromboembolism (VTE).

Body Weight-Based Dosing Of Intravenous Heparin In VTE

Initial Dosing
Loading: 80 U/kg
Maintenance infusion*:18 U/kg/hr(APTT in 6 hrs.)

Subsequent Dose Adjustments

 

Overlapping Heparin And Warfarin During Acute Anticoagulation

Disease Suspected

Give heparin bolus IV


Obtain diagnostic study

Disease Confirmed

• Heparin 80 u/kg IV bolus followed by 18u/kg/hr IV infusion
  
• Obtain APTT at 4-6 hrs and keep APTT in a range that corresponds to a plasma heparin level of 0.2-0.4 u/ml.
  
• Start warfarin on day one at 5 mg and dose daily with the estimated daily maintenance dose or start the estimated daily maintenance dose (2-5 mg.)
• Obtain platelet count every 3-5 days of heparin therapy up to 21 days.
  
• Give heparin and warfarin jointly for 5-7 days. Stop heparin thereafter when PT gives an INR of 2.0-3.0.
  
• Continue warfarin at an INR of 2.0-3.0

 

Managing Bleeding In Patients Receiving Heparin

Minor Bleeding

• Discontinue heparin.
• Monitor vital signs, APTT, Hgb, Hct, platelet count.

Major Bleeding

• Discontinue heparin.
• Monitor vital signs, APTT, Hgb, Hct, platelet count.
• Give blood transfusions as necessary.
• Consider protamine reversal of heparin.

Protamine reversal for patients receiving constant intravenous heparin:

• Give protamine sulfate (1% solution) at 25 mg by slow IV infusion over 15 min.
• Repeat APTT in 20 min. and 1 hr.
• In patients receiving subcutaneous heparin, it may be necessary to repeat the protamine sulfate infusion after 1 hr. because of variable heparin absorption.

Remember

Protamine sulfate can cause severe, anaphylactoid reactions. Use this agent only when severe bleeding warrants it. Have resuscitation equipment nearby.

Heparin Induced Thrombocytopenia, Lepirudin & Argatroban

Standard unfractionated heparin can cause an antibody-mediated (Type II) thrombocytopenia in 2-3% of individuals who receive this drug for longer than 7 days. When the platelet count falls precipitously, STOP heparin. Do not start low-molecular-weight heparin because it will cross-react with the antibody 90% of the time. If a rapidly acting drug is needed, substitute a direct thrombin inhibitor, either lepirudin (Refludan®) or agatroban.

Dosing Lepirudin in Acute Heparin-Induced Thrombocytopenia

• Stop unfractionated heparin
• Do not substitute LMW-heparin
• Hold warfarin

IV infusion (for rapid therapeutic anticoagulation).

• Loading dose: 0.4 mg/kg bolus i.v..
• Maintenance: 0.15 mg/kg/hr i.v. (up to 110 kg body weight
• Adjust maintenance dose to maintain activated partial thromboplastin time (APTT) at 1.5 to 2.5 times the laboratory's mean normal value.

Dosing Argatroban in Acute Heparin-Induced Thrombocytopenia

• Stop unfractionated heparin
• Do not substitute LMW-heparin
• Hold warfarin

IV infusion (for rapid therapeutic anticoagulation)

• Loading dose: no loading dose
• Maintenance: 2 ug/kg/min
• Adjust mainenance dose to maintain APTT at 1.5 to 2.5 times laboratory's mean normal value
  

Give lepirudin or argatrobn for at least 3 days while holding warfarin. When the platelet count has recovered above 100,000/uL, give warfarin at 5 mg/day and adjust dose by INR.

* This outline is intended only for initiating therapy in an emergent situation. Contact the manufacturer of danaparoid (Organon) for details of usage in HIT. On to the thrombolytic therapy page.

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